Variations in the FKBP5 and GLCCI1 genes?both implicated in the GC-GR cascade?have been associated with response to corticosteroid treatment in various diseases.

A total of 165 COPD patients from the HISTORIC study, a double-blind, randomized, placebo-controlled trial, were genotyped for the functional SNVs rs4713916(FKBP5) and rs37973(GLCCI1). Baseline clinical and histological data from endobronchial biopsies, along with patients? responses to inhaled corticosteroids (ICS)?assessed by FEV₁ changes and health-related QoL tests?were examined in relation to the two SNVs.

AG carriers of rs4713916 exhibited a significant FEV₁(ml) improvement in both intergroup and intragroup analyses (p_adj=0.022 and p_adj=0.005, respectively) (Fig.1).

Meanwhile, GG carriers of rs37973 presented with a higher FEV1% predicted at baseline (p=0.003) and continued to show favorable outcomes throughout the study, with positive FEV1 gains after 12 months in both the placebo and control groups, reaching significance only in the ICS treatment control group (p=0.020).

Our findings underscore the importance of genetic variations on response to ICS, revealing key associations and revitalizing interest in personalized medicine in COPD, which has waned due to inconsistencies in recent research.